W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164, United States.
ACS Appl Mater Interfaces. 2020 Nov 25;12(47):52383-52392. doi: 10.1021/acsami.0c14993. Epub 2020 Nov 12.
Traditional infection prevention and treatment methods include synthetic antibiotics, which can cause severe adverse side effects. Carvacrol and thymol are biologically active monoterpenoid extractants from oregano leaves with antibiotic capabilities; however, little is known regarding their effects on bone tissue engineering. The objective of this work is to understand their effects on osteogenesis, specifically with osteoblast and osteoclast cells, from surface-modified Ti6Al4V with plasma sprayed hydroxyapatite (HA) coatings. This system is an alternative to cemented implants to aid in bone healing. Results reveal that full carvacrol release from the HA matrix is successful in aqueous environments and modulation of release kinetics can also be made using polycaprolactone (PCL) and polyethylene glycol (PEG) polymers. From HA-pressed disc samples in physiological pH, full carvacrol release is achieved in 10 days using PCL/PEG, about 95% release in 50 days using no polymer, and 60% in 50 days when using a PCL coating. Without polymer, full carvacrol release is achieved after 3 days from HA coatings in both physiological pH and acidic pH, mimicking the post-surgery environment. The release is assessed as a diffusion-based mechanism in phosphate-buffered saline but degradation-based mechanism in acetate buffer solution. Carvacrol and thymol show bacterial inhibition of and no cytotoxic effects on osteoblast proliferation . Carvacrol and thymol also induce a significant 7% reduction in osteoclast tartrate-resistant acid phosphatase (TRAP) activity, caused by poorly attached cellular morphologies, leading to an approximately 65% reduction in osteoclast resorption pit formation. Our goal is to demonstrate a natural medicinal system that can support bone healing while providing infection prevention and reducing costly revision surgeries for orthopedic and dental applications.
传统的感染预防和治疗方法包括合成抗生素，但其会导致严重的不良反应。香芹酚和百里香酚是从牛至叶中提取的具有抗生素作用的生物活性单萜类提取物；然而，关于它们对骨组织工程的影响知之甚少。本工作的目的是了解它们对成骨的影响，特别是对表面改性的 Ti6Al4V 等离子喷涂羟基磷灰石（HA）涂层上的成骨细胞和破骨细胞的影响。该系统是一种替代骨水泥植入物的方法，有助于骨愈合。结果表明，在水介质中成功实现了香芹酚从 HA 基质中的完全释放，并且可以使用聚己内酯（PCL）和聚乙二醇（PEG）聚合物来调节释放动力学。在生理 pH 值下，从 HA 压片盘样品中，使用 PCL/PEG 可在 10 天内实现完全释放香芹酚，在 50 天内释放约 95%，使用 PCL 涂层则在 50 天内释放 60%。在没有聚合物的情况下，在生理 pH 值和酸性 pH 值下，HA 涂层在 3 天内实现完全释放香芹酚，模拟了手术后的环境。在磷酸盐缓冲盐水（PBS）中，释放被评估为扩散机制，但在醋酸缓冲溶液中则为降解机制。香芹酚和百里香酚对 表现出抑菌作用，对成骨细胞增殖无细胞毒性 。香芹酚和百里香酚还诱导破骨细胞抗酒石酸酸性磷酸酶（TRAP）活性显著降低 7%，这是由于细胞形态附着不良所致，导致破骨细胞吸收陷窝形成减少约 65%。我们的目标是展示一种天然药物系统，该系统既能支持骨愈合，又能提供抗感染作用，并减少骨科和牙科应用中昂贵的翻修手术。
